The Association of Race, Ethnicity, and Insurance Status with the Visual Acuity of Retinoblastoma Survivors in the IRIS® Registry.

PURPOSE: To identify sociodemographic factors associated with the visual outcomes of retinoblastoma survivors. METHODS: Retrospective cohort study using a US-based clinical data registry. All individuals < 18 years of age with a history of retinoblastoma in the Intelligent Research in Sight (IRIS®) Registry (1/1/2013-12/31/2020). The primary outcome was visual acuity below the threshold for legal blindness (20/200 or worse) in at least one eye. Multivariable logistic regression was used to evaluate the association between visual outcomes and age, sex, laterality, race, ethnicity, type of insurance, and geographic location. RESULTS: This analysis included 1545 children with a history of retinoblastoma. The median length of follow-up was 4.1 years (IQR, 2.2-5.9 years) and the median age at most recent clinical visit was 12 years (IQR, 8-16 years). Retinoblastoma was unilateral in 54% of cases. Poor vision in at least one eye was identified in 78% of all children and poor vision in both eyes in 17% of those with bilateral disease. Poor visual outcomes were associated with unilateral diagnosis (OR, 1.55; 95% CI,1.13-2.12; p = .007), Black race (OR, 2.03; 95% CI, 1.19-3.47; p = .010), Hispanic ethnicity (OR, 1.65; 95% CI, 1.16-2.37; p = .006), and non-private insurance (OR, 1.47; 95% CI, 1.02-2.10; p = .037). CONCLUSIONS: Poor visual outcomes appear to be more common among Black, Hispanic, and publicly insured children with a history of retinoblastoma, raising concerns regarding healthcare inequities. Primary care physicians should ensure that young children receive red reflex testing during routine visits and consider retinoblastoma in the differential diagnosis of abnormal eye exams.

Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. METHODS: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010). RESULTS: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time. CONCLUSIONS: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

Causes and Clinical Presentation of Drug-Induced Dermatomyositis: A Systematic Review.

Importance: While several medications are known to induce dermatomyositis (DM), most existing studies are case reports or small case series from a single institution. There is also limited information on DM induced by immune checkpoint inhibitors, which are increasingly used in oncologic therapy. Objective: To characterize causes and clinical presentation of drug-induced DM based on the current literature. Evidence Review: A systematic review was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, from inception to August 22, 2022. Articles meeting preestablished inclusion criteria (written in English and classified as original articles, case reports, literature reviews, and observation letters) were selected and data abstracted. Articles that met the scope of the review were also added from reference lists. When possible, study results were quantitatively combined. Findings: In 134 studies (114 from the literature search and 20 additional studies pulled from reference lists) describing 165 cases, 88 patients (53.3%) were female, and the median (IQR) age was 61 (49-69) years. Among the cases of drug-induced DM, the most common associated medications were hydroxyurea (50 [30.3%]), immune checkpoint inhibitors (27 [16.4%]), statins (22 [13.3%]), penicillamine (10 [6.1%]), and tumor necrosis factor inhibitors (10 [6.1%]). Histopathologic testing, when undertaken, helped establish the diagnosis. There was a median (IQR) of 60 (21-288) days between drug initiation and drug-induced DM onset. History of cancer was reported in 85 cases (51.6%). Conclusions and Relevance: In this systematic review, drug-induced DM was associated with multiple types of medications, including chemotherapies and immunotherapies. It is essential that dermatologists promptly recognize and diagnose drug-induced DM so that they can guide management to minimize interruption of therapy when possible.

Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan.

Background: The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan. Methods: Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses. Results: Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (ß = 0.56, P = .03) and worse HRQOL in work subscale (ß = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (ß = 14.9, P = .002) and diagnosis of hypopituitarism (ß = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (ß = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy. Conclusion: This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.

Approaches to developing de novo cancer population models to examine questions about cancer and race in bladder, gastric, and endometrial cancer and multiple myeloma: the Cancer Intervention and Surveillance Modeling Network incubator program.

BACKGROUND: We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. METHODS: Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population. DISCUSSION: The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality.

Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

PURPOSE: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain. METHODS: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance. RESULTS: In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved). CONCLUSION: Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.

Reassessing the Benefits and Harms of Risk-Reducing Medication Considering the Persistent Risk of Breast Cancer Mortality in Estrogen Receptor-Positive Breast Cancer.

PURPOSE: Recent studies, including a meta-analysis of 88 trials, have shown higher than expected rates of recurrence and death in hormone receptor-positive breast cancer. These new findings suggest a need to re-evaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women. METHODS: We adapted an established Cancer Intervention and Surveillance Modeling Network model to evaluate the lifetime benefits and harms of risk-reducing medication in women with a ≥ 3% 5-year risk of developing breast cancer according to the Breast Cancer Surveillance Consortium risk calculator. Model input parameters were derived from meta-analyses, clinical trials, and large observational data. We evaluated the effects of 5 years of risk-reducing medication (tamoxifen/aromatase inhibitors) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication. The modeled outcomes included invasive breast cancer, breast cancer death, side effects, false positives, and overdiagnosis. We conducted subgroup analyses for individual risk factors such as age, family history, and prior biopsy. RESULTS: Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no tamoxifen or screening. This is equivalent to an absolute reduction of 95 invasive breast cancers, and 42 breast cancer deaths per 1,000 high-risk women. However, these drugs are associated with side effects. For example, tamoxifen could increase the number of endometrial cancers up to 11 per 1,000 high-risk women. Benefits and harms varied by individual characteristics. CONCLUSION: The addition of risk-reducing medication to screening could further decrease the risk of breast cancer death. Clinical guidelines for high-risk women should consider integrating shared decision making for risk-reducing medication and screening on the basis of individual risk factors.

Livedoid vasculopathy.

Livedoid vasculopathy is a painful thrombo-occlusive vascular disorder characterized by spontaneous thrombosis in medium-size arterioles, which causes localized hypoxia and skin ulceration. As livedoid vasculopathy is rare, case reports are the primary means of expanding collective knowledge about its presentation and response to various therapies.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

BACKGROUND: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING: Novo Nordisk.

The Prevalence of Islet Autoantibodies in Children and Adolescents With Type 1 Diabetes Mellitus: A Global Scoping Review.

Background and Purpose: Pancreatic islet autoantibodies (iAb) are the hallmark of autoimmunity in type 1 diabetes. A more comprehensive understanding of the global iAb prevalence could help reduce avertible morbidity and mortality among children and adolescents and contribute to the understanding in the observed differences in the incidence, prevalence and health outcomes of children and adolescents with type 1 diabetes across and within countries. We present the first scoping review that provides a global synthesis of the prevalence of iAb in children and adolescents with type 1 diabetes. Research Design and Methods: We searched Ovid MEDLINE® with Daily Update, Embase (Elsevier, embase.com) and PubMed (National Library of Medicine -NCBI), for studies pertaining to prevalence in children and adolescents (0-19) with type 1 diabetes published between 1 Jan 1990 and 18 June 2021. Results were synthesized using Covidence systematic review software and meta-analysis was completed using R v3·6·1. Two reviewers independently screened abstracts with a third reviewer resolving conflicts (k= 0·92). Results: The review revealed 125 studies from 48 different countries, with 92 from high-income countries. Globally, in new-onset type 1 diabetes, IA-2A was the most prevalent iAb 0·714 [95% CI (0·71, 0·72)], followed by ICA 0·681 [95% CI (0·67, 0·69)], ZnT8A was 0·654 [95% CI (0·64, 0·66)], GADA 0·636 [95% CI (0·63, 0·66)] and then IAA 0·424 [95% CI (0·42, 0·43)], with substantial variation across world regions. The weighted mean prevalence of IA-2A was more variable, highest in Europe at 0·749 [95% CI (0·74, 0·76)] followed by Northern America 0·662 [95% CI (0·64, 0·69)], Latin America and the Caribbean 0·632 [95% CI (0·54, 0·72)], Oceania 0·603 [95% CI (0·54, 0·67)], Asia 0·466 [95% CI (0·44, 0·50)] and Africa 0·311 [95% CI (0·23, 0·40)]. In established cases of type 1 diabetes, GADA was the most prevalent iAb 0·407 [95% CI (0·39, 0·42)] followed by ZnT8A 0·322 [95% CI (0·29, 0·36)], IA-2A 0·302 [95% CI (0·29, 0·32)], IAA 0·258 [95% CI (0·24, 0·26)] and ICA 0·145 [95% CI (0·13, 0·16)], again with substantial variation across world regions. Conclusion: Understanding the global prevalence of iAb in children and adolescents with type 1 diabetes could help with earlier identification of those at-risk of developing type 1 diabetes and inform clinical practice, health policies, resource allocation, and targeted healthcare interventions to better screen, diagnose and manage children and adolescents with type 1 diabetes.

Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants: A Comparative Modeling Analysis.

IMPORTANCE: Screening mammography and magnetic resonance imaging (MRI) are recommended for women with ATM, CHEK2, and PALB2 pathogenic variants. However, there are few data to guide screening regimens for these women. OBJECTIVE: To estimate the benefits and harms of breast cancer screening strategies using mammography and MRI at various start ages for women with ATM, CHEK2, and PALB2 pathogenic variants. DESIGN, SETTING, AND PARTICIPANTS: This comparative modeling analysis used 2 established breast cancer microsimulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) to evaluate different screening strategies. Age-specific breast cancer risks were estimated using aggregated data from the Cancer Risk Estimates Related to Susceptibility (CARRIERS) Consortium for 32 247 cases and 32 544 controls in 12 population-based studies. Data on screening performance for mammography and MRI were estimated from published literature. The models simulated US women with ATM, CHEK2, or PALB2 pathogenic variants born in 1985. INTERVENTIONS: Screening strategies with combinations of annual mammography alone and with MRI starting at age 25, 30, 35, or 40 years until age 74 years. MAIN OUTCOMES AND MEASURES: Estimated lifetime breast cancer mortality reduction, life-years gained, breast cancer deaths averted, total screening examinations, false-positive screenings, and benign biopsies per 1000 women screened. Results are reported as model mean values and ranges. RESULTS: The mean model-estimated lifetime breast cancer risk was 20.9% (18.1%-23.7%) for women with ATM pathogenic variants, 27.6% (23.4%-31.7%) for women with CHEK2 pathogenic variants, and 39.5% (35.6%-43.3%) for women with PALB2 pathogenic variants. Across pathogenic variants, annual mammography alone from 40 to 74 years was estimated to reduce breast cancer mortality by 36.4% (34.6%-38.2%) to 38.5% (37.8%-39.2%) compared with no screening. Screening with annual MRI starting at 35 years followed by annual mammography and MRI at 40 years was estimated to reduce breast cancer mortality by 54.4% (54.2%-54.7%) to 57.6% (57.2%-58.0%), with 4661 (4635-4688) to 5001 (4979-5023) false-positive screenings and 1280 (1272-1287) to 1368 (1362-1374) benign biopsies per 1000 women. Annual MRI starting at 30 years followed by mammography and MRI at 40 years was estimated to reduce mortality by 55.4% (55.3%-55.4%) to 59.5% (58.5%-60.4%), with 5075 (5057-5093) to 5415 (5393-5437) false-positive screenings and 1439 (1429-1449) to 1528 (1517-1538) benign biopsies per 1000 women. When starting MRI at 30 years, initiating annual mammography starting at 30 vs 40 years did not meaningfully reduce mean mortality rates (0.1% [0.1%-0.2%] to 0.3% [0.2%-0.3%]) but was estimated to add 649 (602-695) to 650 (603-696) false-positive screenings and 58 (41-76) to 59 (41-76) benign biopsies per 1000 women. CONCLUSIONS AND RELEVANCE: This analysis suggests that annual MRI screening starting at 30 to 35 years followed by annual MRI and mammography at 40 years may reduce breast cancer mortality by more than 50% for women with ATM, CHEK2, and PALB2 pathogenic variants. In the setting of MRI screening, mammography prior to 40 years may offer little additional benefit.

Incidence and prevalence of type 1 diabetes and diabetic ketoacidosis in children and adolescents (0-19 years) in Thailand (2015-2020): A nationwide population-based study.

BACKGROUND: There is a lack of published studies on incidence of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) in Thailand. We aimed to estimate the national prevalence and incidence of T1D and DKA. METHODS: Using Thailand's nationwide population-based longitudinal data covering 69 million individuals, we included the entire children and adolescents recorded in the database. Diseases were identified using ICD-10 codes. We investigated the prevalence of T1D and cumulative incidence of T1D, T1D referral, DKA, and mortality risk of DKA in five years from 2015 to 2020. T1D and DKA annual incidence were also estimated. We present findings for the total population and by sex, age, and urban-rural residencies. FINDINGS: A total of 19,784,781 individuals aged less than 20 years were identified in 2015. The crude T1D prevalence in 2015 was 17·6 per 100,000 and crude T1D incidence rate was 5·0 per 100,000. T1D prevalence and cumulative incidence were significantly higher in older children (p < 0·001) and females (p < 0·001) than their counterparts. Among those with T1D, cumulative incidence of T1D referral was 42·4%. It was highest amongst children aged 5-14 years and was significantly higher among females (all p < 0·05). The crude DKA incidence rate at any point after diagnosis was 10·8%. The cumulative incidence of DKA was significantly higher in females and peaked in individuals aged 5-14 years (all p < 0·001). The DKA mortality risk was 258·2 per 100,000. INTERPRETATION: Older children and females had higher T1D prevalence. The DKA cumulative incidence and mortality risk were relatively low, and such incidence was peak in individuals aged 5-14 years. FUNDING: Harvard University.

Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research.

BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS). METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS. RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million). CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.

Variation in the incidence of type 1 diabetes mellitus in children and adolescents by world region and country income group: A scoping review.

INTRODUCTION: Around 18.7 million of the 537 million people with diabetes worldwide live in low-income and middle-income countries (LMIC), where there is also an increase in the number of children, adolescents, and young adults diagnosed with type 1 diabetes (T1D). There are substantial gaps in data in the current understanding of the epidemiological patterns and trends in incidence rates of T1D at the global level. METHODS: We performed a scoping review of published studies that established the incidence of T1D in children, adolescents, and young adults aged 0-25 years at national and sub-national levels using PubMed, Embase and Global Health. Data was analyzed using R programming. RESULTS: The scoping review identified 237 studies which included T1D incidence estimates from 92 countries, revealing substantial variability in the annual incidence of T1D by age, geographic region, and country-income classification. Highest rates were reported in the 5-9 and 10-14 year age groups than in the 0-4 and 15-19 year age groups, respectively. In the 0-14 year age group, the highest incidence was reported in Northern Europe (23.96 per 100,000), Australia/New Zealand (22.8 per 100,000), and Northern America (18.02 per 100,000), while the lowest was observed in Melanesia, Western Africa, and South America (all < 1 per 100,000). For the 0-19 year age group, the highest incidence was reported in Northern Europe (39.0 per 100,000), Northern America (20.07 per 100,000), and Northern Africa (10.1 per 100,000), while the lowest was observed in Eastern and Western Africa (< 2 per 100,000). Higher incidence rates were observed in high-income countries compared to LMICs. There was a paucity of published studies focusing on determining the incidence of T1D in LMICs. CONCLUSION: The review reveals substantial variability in incidence rates of T1D by geographic region, country income group, and age. There is a dearth of information on T1D in LMICs, particularly in sub-Saharan Africa, where incidence remains largely unknown. Investment in population-based registries and longitudinal cohort studies could help improve the current understanding of the epidemiological trends and help inform health policy, resource allocation, and targeted interventions to enhance access to effective, efficient, equitable, and responsive healthcare services.

Small lymphocytic lymphoma presenting as chronic diffuse lip swelling.

Although rare, small lymphocytic lymphoma can present as chronic lip swelling and papules, thus mimicking the features of orofacial granulomatosis, a chronic inflammatory disorder characterized by subepithelial noncaseating granulomas, or papular mucinosis, characterized by localized dermal mucin deposition of mucin. When assessing lip swelling, one must carefully consider the clinical clues and have a low threshold to perform a diagnostic tissue biopsy, preventing delays in treatment or progression of the lymphoma.

Estimating Treatment-Switching Bias in a Randomized Clinical Trial of Ovarian Cancer Treatment: Combining Causal Inference with Decision-Analytic Modeling.

BACKGROUND: Bevacizumab is efficacious in delaying ovarian cancer progression and controlling ascites. The ICON7 trial showed a significant benefit in overall survival for bevacizumab, whereas the GOG-218 trial did not. GOG-218 allowed control group patients to switch to bevacizumab upon progression, which may have biased the results. Lack of data on switching behavior prevented the application of g-methods to adjust for switching. The objective of this study was to apply decision-analytic modeling to estimate the impact of switching bias on causal treatment-effect estimates. METHODS: We developed a causal decision-analytic Markov model (CDAMM) to emulate the GOG-218 trial and estimate overall survival. CDAMM input parameters were based on data from randomized clinical trials and the published literature. Overall switching proportion was based on GOG-218 trial information, whereas the proportion switching with and without ascites was estimated using calibration. We estimated the counterfactual treatment effect that would have been observed had no switching occurred by denying switching in the CDAMM. RESULTS: The survival curves generated by the CDAMM matched well with the ones reported in the GOG-218 trial. The survival curve correcting for switching showed an estimated bias such that 79% of the true treatment effect could not be observed in the GOG-218 trial. Results were most sensitive to changes in the proportion progressing with severe ascites and mortality. LIMITATIONS: We used a simplified model structure and based model parameters on published data and assumptions. Robustness of the CDAMM was tested and model assumptions transparently reported. CONCLUSIONS: Medical-decision science methods may be merged with empirical methods of causal inference to integrate data from other sources where empirical data are not sufficient. We recommend collecting sufficient information on switching behavior when switching cannot be avoided.

Cardiac Enhanced Recovery After Surgery: Early Outcomes in a Community Setting.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs have demonstrated improved outcomes in noncardiac surgery. More recently, ERAS has been applied to cardiac surgery with promising results. We have implemented cardiac ERAS at our community-based program, aiming to improve all phases of care, and now report our early results. METHODS: We retrospectively analyzed 73 consecutive patients treated with ERAS care compared with 74 patients treated before implementing ERAS. Our ERAS program consisted of 6 perioperative care bundles including enhanced patient education, shortened preoperative fasting period and oral carbohydrate load, postoperative nausea prophylaxis, multimodal opioid-sparing analgesia, early extubation, and early mobilization. RESULTS: ERAS patients required significantly less opioids captured as total morphine milligram equivalents (MME) (median 35.0 vs 75.3; P < .001), less nausea as determined by fewer total ondansetron rescue doses (median 0 vs 0.5; P = .011), and less lightheadedness (P = .028) compared with pre-ERAS patients. Postoperative mobility was significantly better (postoperative day 4: 95% vs 81%; P = .013) and postoperative length of stay was lower for ERAS care but did not reach statistical significance (median 4 days vs 5 days; P = .06). There was no difference in pain or glucose control or in early extubation. CONCLUSIONS: Cardiac ERAS significantly decreased opioid use, nausea, and lightheadedness and improved functional outcome for cardiac surgical patients in a community hospital.